Cancer has become an all-pervasive threat to a society with an ever-increasing elderly population. In addition to the numerous cancers which are genetically determined, cancers resulting from contacts with mutagens or other neoplastic-inducing agents, there is the additional factor that as the population ages, the likelihood of cells becoming cancerous appears to increase. Therefore, there has been ever-increasing efforts to find treatments which are capable of controlling tumor growth, reducing tumor burden and inhibiting metastasis. In view of the great diversity of types of cancers, the differing cellular mechanisms associated with a particular type of cancer, and the apparent differences in response of tumors to different agents, no one agent would appear to be satisfactory in the treatment of neoplasia. Because cancer cells are cells of the host whose phenotype has changed, resulting in uncontrolled growth and lack of differentiation, it has been very difficult to develop agents which can distinguish between normal host cells and the neoplastic cells.
The primary target has been cells which are rapidly proliferating. While this group of cells includes the neoplastic cells, it also includes leukocytes, which are essential to the immune system. However, in view of the morbidity associated with cancer, irradiation and chemotherapeutic approaches have been the primary therapeutic modality.
While for the most part the cytotoxic compounds have been synthetic organic compounds, there has also been interest in some naturally occurring compounds, which appear to have anti-tumor effect. One of these compounds is tumor necrosis factor ("TNF"), which includes TNF-.alpha. and -.beta.. Where TNF is used, it is intended that either or both TNF-.alpha. and -.beta. are intended. While TNF is active against tumor cells, it also has a broad spectrum of other physiological activities, so as to have substantial side effects. However, the promise of using TNF has encouraged investigations in ways in which TNF may be employed, while reducing the level of side effects associated with a TNF-based therapy.